Glucagon antagonists

A - Human Necessities – 61 – K

Patent

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Details

A61K 38/26 (2006.01) A61K 38/16 (2006.01) A61K 47/48 (2006.01) A61P 3/04 (2006.01) A61P 3/10 (2006.01) C07K 14/605 (2006.01) C07K 17/08 (2006.01) C07K 19/00 (2006.01)

Patent

CA 2707861

Glucagon antagonists are provided which comprise amino acid substitutions and/or chemical modifications to glucagon sequence. In one embodiment, the glucagon antagonists comprise a native glucagon peptide that has been modified by the deletion of first two to five amino acid residues from the N-terminus and (i) an amino acid substitution at position 9 (according to the numbering of native glucagon) or (ii) substitution of the Phe at position 6 (according to the numbering of native glucagon) with phenyl lactic acid (PLA). In another embodiment, the glucagon antagonists comprise the structure A-B-C as described herein, wherein A is PLA, an oxy derivative thereof, or a peptide of 2-6 amino acids in which two consecutive amino acids of the peptide are linked via ester or ester bond. Image

L'invention concerne des antagonistes du glucagon comprenant des substitutions d'acides aminés et/ou des modifications chimiques de la séquence de glucagon. Dans un mode de réalisation, les antagonistes du glucagon comprennent un peptide de glucagon natif qui a été modifié par suppression des deux premiers résidus d'acides aminés provenant de la terminaison N et (i) une substitution d'acides aminés à la position 9 (selon le numérotage d'un glucagon natif) ou (ii) une substitution du Phe à la position 6 (selon le numérotage d'un glucagon natif) par un acide lactique phénylique (PLA). Dans un autre mode de réalisation, les antagonistes du glucagon comprennent la structure A-B-C précitée, dans laquelle A représente PLA, un dérivé oxy de celui-ci ou un peptide de 2-6 acides aminés dans lequel deux acides aminés consécutifs du peptide sont liés via une liaison ester ou éther.

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